Tuesday, February 1, 2011
ppGpp mediates cross-talk between the stringent and acid stress responses
We know that stringent response alarmone ppGpp can do about anything, interacting with RNA Polymerase, translational GTPases, Obg GTPase, polynucleotide phosphorylase, DnaG primase, IMP dehydrogenase and adenylosuccinate synthetase to name a few. In net result is: production of ribosomes and tRNAs is halted, cell cycle is arrested, and amino acids are produced.
Well, now one more target was discovered, lysine decarboxylase Ldc1/CadA. Lysine decarboxylase is induced upon acid stress conditions and protects the cell catalyzing decarboxylation of L-lysine resulting in the polyamine cadaverine and carbon dioxide. CO2 diffuses away and basic cadaverine keeps the intracellular pH, protecting from acidification.
Kanjee at al. solved the Lcd1 x-ray strucutre, and the protein turned out to be in complex with ppGpp. Enzymatic assays showed that ppGpp inhibits Lcd1, thus providing a link between the acid and stringent responses: these two are in a sense are mutually exclusive. During the stringent response ppGpp alters RNA Polymerase in such a way that genes involved in amino acid biosynthesis are predominantly transcribed, and during the acid stress response Lcd1 degrades lysine. Inhibition of Ldl1 by ppGpp stops amino acid degradation, shifting the balance even more towards the amino acid production.
Kanjee U, Gutsche I, Alexopoulos E, Zhao B, El Bakkouri M, Thibault G, Liu K, Ramachandran S, Snider J, Pai EF, & Houry WA (2011). Linkage between the bacterial acid stress and stringent responses: the structure of the inducible lysine decarboxylase. The EMBO journal PMID: 21278708
Mendeley group on stringent response